This real-word study is designed to prospectively explore whether local treatment (surgery, ablation, radiotherapy and others) can prolong the time to treatment discontinuation during 1L lorlatinib treatment in Chinese patients with unresectable ALK+ NSCLC. Participation in this study is not intended to change the routine treatment received as determined by their attending physicians. Patients will be treated according to the routine medical practice in terms of visit frequency and types of assessments performed.

1 Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:

1.1. Diagnosis:

1. Study Population: Patients with histologically or cytologically confirmed diagnosis of locally advanced [(Stage IIIB/C not amenable for multimodality treatment) or metastatic (Stage IV) by American Joint Committee on Cancer (AJCC) v 7.0] ALK-positive NSCLC where ALK status is determined by the Ventana ALK (D5F3) Companion Diagnostic (CDx) IHC test performed on the Ventana ULTRA or XT Platforms, FISH, PCR, or next generation sequencing (NGS), or circulating tumor DNA (ctDNA).
2. Tumor Requirements: At least 1 measurable target lesion per RECIST v. 1.1 that has not been previously irradiated. Brain metastases are allowed.

1.2. No prior systemic treatment for advanced (Stage IIIB/C not amenable for multimodality treatment) or metastatic (Stage IV) disease.

1.3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, 2 or 3.

1.4. Age ≥18 years. 1.5. Adequate Liver Function, including:

1. Total serum bilirubin ≤1.5 x ULN;
2. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN (≤5.0 x ULN in case of liver metastases).

1.6. Life expectancy at least 6 months. 1.7. Serum pregnancy test (for females of childbearing potential) negative at screening. Female patients of non-childbearing potential must meet at least 1 of the following criteria:

1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause (which may be confirmed with a serum follicle-stimulating hormone [FSH] level confirming the postmenopausal state if appropriate);
2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
3. Have medically confirmed ovarian failure. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential. 1.8. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study.

1.9. Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures. 2.Exclusion Criteria

Subjects presenting with any of the following characteristics/conditions will not be included in this clinical study:

2.1. Major surgery within 4 weeks prior to randomization. Minor surgical procedures (e.g., port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.

2.2. Radiation therapy within 2 weeks prior to enrollment, including stereotactic or partial brain irradiation. Patients who complete whole brain irradiation within 4 weeks prior to randomization or palliative radiation therapy outside of the CNS within 48 hours prior to randomization will also not be included in the study.

2.3. Gastrointestinal abnormalities, including inability to take oral medication; requirement for intravenous alimentation; prior surgical procedures affecting absorption including total gastric resection or lap band; active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease; treatment for active peptic ulcer disease in the past 6 months; malabsorption syndromes.

2.4. Known prior or suspected severe hypersensitivity to study drugs or any component in their formulations.

2.5. History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis.

2.6. Evidence of active malignancy (other than NSCLC, non-melanoma skin cancer, or localized prostate cancer or any in situ cancer which does not currently require treatment) within the last 3 years prior to randomization.

2.7. Concurrent use of any of the following food or drugs (consult the sponsor if in doubt whether a food or a drug fall into any of the above categories) within 12 days prior to the first dose of lorlatinib.

1. Known strong CYP3A inhibitors (e.g., strong CYP3A inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits [eg, Seville oranges, pomelos], boceprevir, cobicistat, conivaptan, itraconazole, ketoconazole, posaconazole, ritonavir alone and with danoprevir or elvitegravir or indinavir or lopinavir or paritaprevir or ombitasvir or dasabuvir or saquinavir or tipranavir, telaprevir, troleandomycin, and voriconazole. The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.
2. Known CYP3A substrates with narrow therapeutic index, such as astemizole*, terfenadine*, cisapride*, pimozide, quinidine, tacrolimus, cyclosporine, sirolimus, alfentanil, fentanyl (including transdermal patch) or ergot alkaloids (ergotamine, dihydroergotamine) (*withdrawn from US market).
3. Known strong CYP3A inducers (e.g., carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's Wort). d. Known P-gp substrates with a narrow therapeutic index (e.g., digoxin).

2.8. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

2.9. Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.

Patients with histologically or cytologically confirmed diagnosis of locally advanced [(Stage IIIB/C not amenable for multimodality treatment) or metastatic (Stage IV) by American Joint Committee on Cancer (AJCC) v 7.0] ALK-positive NSCLC where ALK status is determined by the Ventana ALK (D5F3) Companion Diagnostic (CDx) IHC test performed on the Ventana ULTRA or XT Platforms, FISH, PCR, or next generation sequencing (NGS), or circulating tumor DNA (ctDNA).